A significant challenge for the design and development of peptide-based therapy, such as immunotherapy, is the intracellular delivery of the peptides to intracellular compartments. An example of this is the need to deliver antigen peptides to the antigen processing machinery such that the peptides are presented bound to a class I MHC molecule and thereby stimulate a CTL response. Other examples include delivery of peptide-based drugs to intracellular drug targets. In particular, free peptides often display poor uptake by cells.
One approach that has been employed to date, is to deliver peptides to a intracellular location by administering a vector, such as a viral vector, containing a polynucleotide that encodes the peptide of choice such the that cell can be transfected with the vector and the peptide is produced by the cellular translational machinery. A further example of a strategy to deliver a peptide to an intracellular location is described in Muders et al., 2009, Clin Cancer Res, Vol. 15(12), pp. 4095-4103, in which a GIPC-PDZ-targeting peptide was delivered to certain pancreatic tumour cells. The peptide was modified by N-terminal myristolation.
However, there remains a need for further methods and compositions for intracellular delivery of peptides, e.g., in order to induce an immune response or for the administration of certain peptide-based drugs. The present invention addresses these and other needs.
WO 2006/037979 describes nanoparticles comprising antigens and adjuvants, and immunogenic structures comprising the nanoparticles.